title: Early joint tissue changes are highly correlated with a set of inflammatory and degradative synovial biomarkers after ACL autograft and its sham surgery in an ovine model.
abstract: While impossible in humans, the mechanisms of early cartilage, bone and meniscal damage can be quantified after anterior cruciate ligament (ACL) injury in animal models. We utilized an ovine model to determine if the mRNA expression of inflammatory and degradative molecules (IL-1β, IL-6, MMP-1, 2, 3, and 13) in the synovium correlated to changes in joint tissues 2 weeks post-ACL surgery, to test the hypothesis that synovial inflammation is a marker of these changes and possibly their originator. Nine "idealized" ACL autografts were performed and compared with three sham and six normal animals. Using validated protocols, early osteophyte formation, articular cartilage, and meniscal damage were quantified. Synovium was harvested and mRNA expression quantified using qPCR. Multiple linear regression analysis (MLRA) was utilized to correlate synovial mRNA expression in treated and contra-lateral limbs, from all treatment groups with corresponding joint scores. Synovial mRNA expression was significantly elevated in all experimental and sham joints. The MLRA model was a significant predictive tool (p = 0.001, R(2)  = 0.70) of gross tissue scores with significant contributions from IL-1β, IL-6, and MMP-3. Findings suggest that this set of synovial biomarkers is predictive (p < 0.009) of early gross changes of joint tissues after arthrotomy and likely directly involved in the relevant mechanisms, particularly early osteophyte formation, in vivo.
authors.affiliation: McCaig Institute for Bone and Joint Health, Faculty of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, Canada T2N 4N1.
authors.forename: Bryan J
authors.initials: BJ
authors.lastname: Heard
authors.forename: Yamini
authors.initials: Y
authors.lastname: Achari
authors.forename: May
authors.initials: M
authors.lastname: Chung
authors.forename: Nigel G
authors.initials: NG
authors.lastname: Shrive
authors.forename: Cyril B
authors.initials: CB
authors.lastname: Frank
mesh_terms: D000818:Animals; D016118:Anterior Cruciate Ligament / Q000637:transplantation*; D015415:Biomarkers / Q000378:metabolism*; D005260:Female; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007718:Knee Injuries / Q000378:metabolism / Q000473:pathology*; D007719:Knee Joint / Q000378:metabolism / Q000473:pathology*; D016014:Linear Models; D053505:Matrix Metalloproteinases, Secreted / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012756:Sheep; D013583:Synovial Membrane / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D053505:Matrix Metalloproteinases, Secreted